LC对非小细胞肺癌放疗增敏的作用及其机制研究  

The study of effect and mechanism of LC on radiotherapy sensitization in non-small cell lung cancer

作　　者：陈素梅 朱鲁程 许雅思 张仕蓉 马胜林[2] Chen Sumei

机构地区：[1]浙江大学医学院附属杭州市肿瘤医院,杭州市肿瘤研究所附属杭州市肿瘤医院,310002 [2]杭州市第一人民医院转化医学研究中心,310003

出　　处：《浙江临床医学》2023年第10期1434-1437,共4页Zhejiang Clinical Medical Journal

基　　金：浙江省中医药科技计划项目(2018ZY009,2020ZB195)。

摘　　要：目的放疗是肺癌最常用的治疗手段之一,化疗药物可增强放疗敏感性,但相关毒副作用及耐药的产生严重影响放疗疗效,因此,寻找新型放疗增敏药物具有重要的现实意义。方法MTS法分析细梗香草总皂苷(LC)对肺癌细胞增殖的影响,集落形成实验、流式细胞术检测LC联合放疗后细胞集落形成率和凋亡的情况,Western blot和小干扰RNA探索其放疗增敏作用分子机制。结果MTS示LC对肺癌细胞株有增殖抑制作用,呈剂量和时间依赖性,同时其还增强放疗诱导的细胞增殖抑制和凋亡潜能。LC与放疗联合放射增敏比均>1.0,联合指数<1.0,表明二者具有协同作用。Western blot示LC调控非同源末端连接过程中相关蛋白的表达水平,小干扰RNA下调DNA-PKcs的表达后,LC的放疗增敏作用减弱。结论在非小细胞肺癌中LC通过抑制DNA损伤修复过程中的非同源末端连接而发挥放疗增敏作用。Objective Radiotherapy is one of the most common treatments for lung cancer.Traditional chemotherapeutic drugs could enhance radiosensitivity,but the related side effects and drug resistance seriously affect the treatment of lung cancer.Therefore,it is important to discover new radiosensitizers with high efficiency and low toxicity.Methods Proliferation inhibition by LC capilliposide was assessed by MTS assay.The colony formation assay and flow cytometry detected the cell colony formation rate and apoptosis after LC capilliposide combined with radiotherapy,and Western blot and small interfering RNA explored the molecular mechanism of radiotherapy sensitization.Results MTS showed that LC capilliposide inhibited cell proliferation in a dose-and time-dependent manner,while it also enhanced the cell proliferation inhibition and apoptotic potential induced by radiotherapy.The combination of LC capilliposide and radiotherapy showed a radiosensitization enhancement ratio greater than 1.0.The combination index values was less than 1.0,indicating that the two are synergistic.Western blot analysis showed that treatment LC capilliposide could regulate the expression levels of proteins during the non-homologous end-joining process.After downregulating the expression of DNA-PKcs with small interfering RNA,the radiosensitization effect of LC was reduced.Conclusion LC capilliposide exerts radiotherapy sensitization in non-small cell lung cancer by inhibiting non-homologous end joining during DNA damage repair.

关 键 词：细梗香草总皂苷 非同源末端连接 放疗增敏 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]